Identification
- Summary
Fulvestrant is an estrogen receptor antagonist used to treat HR+ breast cancer that may also be HER2-.
- Brand Names
- Faslodex
- Generic Name
- Fulvestrant
- DrugBank Accession Number
- DB00947
- Background
Fulvestrant is a drug treatment of hormone receptor (HR)-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. While it is used as monotherapy for the treatment of breast cancers, it is also used in combination with alpelisib for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Fulvestrant (DB00947)
- Weight
- Average: 606.78
Monoisotopic: 606.316607362 - Chemical Formula
- C32H47F5O3S
- Synonyms
- (7α,17β)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1(10),2,4-triene-3,17-diol
- Fulvestrant
- External IDs
- ICI 182,780
- ICI 182780
- ICI-182780
- ZD-9238
- ZD9238
Pharmacology
- Indication
For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy, as monotherapy or in combination with other antineoplastic agents.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Advanced breast cancer •••••••••••• •••••••••••••• ••••• ••••••••• •••••••• •••••••••••• ••••••• ••••••••• Treatment of Advanced breast cancer •••••••••••• •••••••••••••• ••••••••• Used in combination to treat Advanced or metastatic breast cancer Regimen in combination with: Alpelisib (DB12015) •••••••••••• •••••••••••••• •••••• •••• ••••••••• ••••••• ••••••••••• ••••• ••••••••• ••••••• ••••••••• Used in combination to treat Advanced or metastatic breast cancer Regimen in combination with: Alpelisib (DB12015) •••••••••••• ••••••• ••••••••••• ••••• ••••••••• •••••••• •••• •••• •••••••• ••••••••• Used in combination to treat Advanced or metastatic breast cancer Regimen in combination with: Abemaciclib (DB12001) •••••••••••• ••••• ••••••••• •••••••• •••••••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
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Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.
- Mechanism of action
Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines.
Target Actions Organism AEstrogen receptor alpha antagonistHumans - Absorption
Not Available
- Volume of distribution
- 3 to 5 L/kg
- Protein binding
99% (mainly VLDL, LDL, and HDL)
- Metabolism
Metabolism of fulvestrant appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3 and 17 positions of the steroid nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models. Studies using human liver preparations and recombinant human enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown.
- Route of elimination
Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%). Renal elimination was negligible (less than 1%).
- Half-life
40 days
- Clearance
Not Available
- Adverse Effects
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There is no clinical experience with overdosage in humans.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAdenine The metabolism of Fulvestrant can be decreased when combined with Adenine. Ambroxol The risk or severity of methemoglobinemia can be increased when Fulvestrant is combined with Ambroxol. Amitriptyline The metabolism of Fulvestrant can be decreased when combined with Amitriptyline. Articaine The risk or severity of methemoglobinemia can be increased when Fulvestrant is combined with Articaine. Asciminib The metabolism of Fulvestrant can be decreased when combined with Asciminib. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Fulvestrant Solution 50 mg / mL Intramuscular Actavis Pharma Company Not applicable Not applicable Canada 
Faslodex Injection, solution 250 mg/5ml Intramuscular Astra Zeneca Ab 2016-09-20 Not applicable EU 
Faslodex Solution 50 mg / mL Intramuscular Astra Zeneca 2004-06-14 Not applicable Canada Faslodex Injection 50 mg/1mL Intramuscular AstraZeneca Pharmaceuticals LP 2010-11-01 Not applicable US 
Faslodex Injection, solution 250 mg/5ml Intramuscular Astra Zeneca Ab 2016-09-20 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-fulvestrant Solution 50 mg / mL Intramuscular Apotex Corporation Not applicable Not applicable Canada Fulvestrant Injection 50 mg/1mL Intramuscular Sandoz Inc 2023-07-01 Not applicable US Fulvestrant Injection, solution 50 mg/1mL Intramuscular Zydus Lifesciences Limited 2021-12-14 Not applicable US Fulvestrant Injection 50 mg/1mL Intramuscular Sandoz Inc 2019-05-29 Not applicable US Fulvestrant Injection 50 mg/1mL Intramuscular HBT Labs, Inc. 2019-11-21 Not applicable US
Categories
- ATC Codes
- L02BA03 — Fulvestrant
- Drug Categories
- Anti-Estrogens
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Endocrine Therapy
- Estradiol Congeners
- Estranes
- Estrenes
- Estrogen Antagonists
- Estrogen Receptor Antagonists
- Fused-Ring Compounds
- Gonadal Hormones
- Gonadal Steroid Hormones
- Hormone Antagonists
- Hormone Antagonists and Related Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Selective Estrogen Receptor Modulators
- Steroids
- UGT1A1 Substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Estrane steroids
- Direct Parent
- Estrogens and derivatives
- Alternative Parents
- 3-hydroxysteroids / 17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / 1-hydroxy-2-unsubstituted benzenoids / Sulfoxides / Secondary alcohols / Cyclic alcohols and derivatives / Sulfinyl compounds / Organofluorides show 3 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 17-hydroxysteroid / 3-hydroxysteroid / Alcohol / Alkyl fluoride / Alkyl halide / Aromatic homopolycyclic compound / Benzenoid / Cyclic alcohol / Estrogen-skeleton show 13 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 22X328QOC4
- CAS number
- 129453-61-8
- InChI Key
- VWUXBMIQPBEWFH-WCCTWKNTSA-N
- InChI
- InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1
- IUPAC Name
- (1S,3aS,3bR,4R,9bS,11aS)-11a-methyl-4-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-diol
- SMILES
- [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H]
References
- General References
- Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36. [Article]
- Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. doi: 10.1517/14656561003641982. [Article]
- Bross PF, Cohen MH, Williams GA, Pazdur R: FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477-80. [Article]
- External Links
- Human Metabolome Database
- HMDB0015082
- KEGG Drug
- D01161
- PubChem Compound
- 17756771
- PubChem Substance
- 46508664
- ChemSpider
- 94553
- BindingDB
- 50238741
- 282357
- ChEBI
- 31638
- ChEMBL
- CHEMBL1358
- Therapeutic Targets Database
- DAP000319
- PharmGKB
- PA164747170
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Fulvestrant
- FDA label
- Download (520 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Other Locally Advanced or / Metastatic Breast Cancer 1 4 Completed Treatment Breast Neoplasms / Metastatic Cancer 1 4 Not Yet Recruiting Treatment Breast Cancer 1 4 Recruiting Treatment Advanced Breast Cancer 1 4 Recruiting Treatment Hormone Receptor-positive Metastatic Breast Cancer / Metastatic HER2 Negative Breast Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Astrazeneca pharmaceuticals lp
- Packagers
- AstraZeneca Inc.
- Vetter Pharma Fertigung GmbH and Co. KG
- Dosage Forms
Form Route Strength Injection Intramuscular Injection, solution Intramuscular; Parenteral 250 MG/5ML Solution Intramuscular 50 mg / mL Solution Parenteral 0.250 g Injection, solution Intramuscular 50 mg/ml Injection, solution Intramuscular Solution Intramuscular 250.00 mg Injection Intramuscular 250 mg/5mL Injection Intramuscular 50 mg/1mL Injection Intravenous 50 mg/1mL Injection, solution Intramuscular 250 mg/5mL Injection, solution Intramuscular 50 mg/1mL Solution Intramuscular 250 mg Injection, solution Parenteral Injection, solution Intramuscular 250 mg Injection, solution Intramuscular; Parenteral 250 MG Injection, solution Parenteral 250 mg Injection, solution Injection, solution 250 MG Injection, solution Parenteral 250 mg/5ml Solution Intramuscular 250.000 mg Solution Intramuscular 250 mg/5ml Injection, solution 250 mg/5ml - Prices
Unit description Cost Unit Faslodex 125 mg/2.5 ml syringe 240.83USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2351004 No 2003-02-18 2021-01-08 Canada US6774122 Yes 2004-08-10 2021-07-09 US US7456160 Yes 2008-11-25 2021-07-09 US US8329680 Yes 2012-12-11 2021-07-09 US US8466139 Yes 2013-06-18 2021-07-09 US US10188663 No 2019-01-29 2034-02-14 US US9271990 No 2016-03-01 2034-05-17 US US9833459 No 2017-12-05 2034-02-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 8.9 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00672 mg/mL ALOGPS logP 6.54 ALOGPS logP 7.57 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 10.32 Chemaxon pKa (Strongest Basic) -0.88 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 57.53 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 155.34 m3·mol-1 Chemaxon Polarizability 65.88 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9217 Caco-2 permeable - 0.5095 P-glycoprotein substrate Substrate 0.722 P-glycoprotein inhibitor I Non-inhibitor 0.6251 P-glycoprotein inhibitor II Non-inhibitor 0.967 Renal organic cation transporter Non-inhibitor 0.7568 CYP450 2C9 substrate Non-substrate 0.7667 CYP450 2D6 substrate Non-substrate 0.7737 CYP450 3A4 substrate Substrate 0.6945 CYP450 1A2 substrate Non-inhibitor 0.6842 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.658 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6701 Ames test Non AMES toxic 0.6318 Carcinogenicity Non-carcinogens 0.75 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6310 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6158 hERG inhibition (predictor II) Inhibitor 0.7955
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 264.2973517 predictedDarkChem Lite v0.1.0 [M-H]- 241.36281 predictedDeepCCS 1.0 (2019) [M+H]+ 264.4617517 predictedDarkChem Lite v0.1.0 [M+H]+ 243.70566 predictedDeepCCS 1.0 (2019) [M+Na]+ 262.6989517 predictedDarkChem Lite v0.1.0 [M+Na]+ 249.56682 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Curran M, Wiseman L: Fulvestrant. Drugs. 2001;61(6):807-13; discussion 814. [Article]
- Elkak AE, Mokbel K: Pure antiestrogens and breast cancer. Curr Med Res Opin. 2001;17(4):282-9. [Article]
- Dow KH: Existing and emerging endocrine therapies for breast cancer. Cancer Nurs. 2002 Apr;25 Suppl 2:6S-11S. [Article]
- Bundred N, Howell A: Fulvestrant (Faslodex): current status in the therapy of breast cancer. Expert Rev Anticancer Ther. 2002 Apr;2(2):151-60. [Article]
- Morris C, Wakeling A: Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy. Endocr Relat Cancer. 2002 Dec;9(4):267-76. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. doi: 10.1517/14656561003641982. [Article]
- McKeage K, Curran MP, Plosker GL: Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Drugs. 2004;64(6):633-48. [Article]
- Jones SE, Pippen J: Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer. Clin Breast Cancer. 2005 Apr;6 Suppl 1:S9-14. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- The FDA label for Fluvesrant indicates that this enzyme action is unlikely to be involved in any drug interactions. No dose adjustments are recommended.
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Robertson JF, Harrison M: Fulvestrant: pharmacokinetics and pharmacology. Br J Cancer. 2004 Mar;90 Suppl 1:S7-10. doi: 10.1038/sj.bjc.6601630. [Article]
- Rocca A, Maltoni R, Bravaccini S, Donati C, Andreis D: Clinical utility of fulvestrant in the treatment of breast cancer: a report on the emerging clinical evidence. Cancer Manag Res. 2018 Aug 30;10:3083-3099. doi: 10.2147/CMAR.S137772. eCollection 2018. [Article]
- Fluvestrant FDA label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- Dancygier H. (2010). Clinical Hepatology. Springer-Verlag. [ISBN:978-3-642-04509-7]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54